1. Technical Field
The present invention is related to a vaccine against rotavirus diseases. More particularly, the invention is related to the use of a live rhesus rotavirus attenuated in humans and which can be used as a vaccine in humans to prevent or control diseases caused by human rotaviruses.
2. State of the Art
Diarrheal disease is an important cause of morbidity in infants and young children in developed countries and is a major cause of morbidity and mortality in the same age group in developing countries. The extent of the problem of gastroenteritis in the United States was highlighted during a 10-year study of a group of Cleveland families in which infectious gastroenteritis was found to be the second most common disease experience, accounting for 16% of approximately 25,000 illnesses. The toll from diarrheal diseases in the developing countries is even more staggering. It has been estimated that in Asia, Africa, and Latin America 3-5 billion cases of diarrhea and 5-10 million diarrhea-associated deaths occur each year. In addition, diarrhea ranked first in the categories of frequency of disease and mortality. Moreover, from a summary of selected studies, it was estimated that 744 million to 1 billion episodes of diarrhea and 4.6 million deaths from diarrhea occur in children under 5 years of age in these regions, excluding China.
The discovery in 1972 of the 27-nm Norwalk virus and its association with epidemic viral gastroenteritis in older children and adults and the discovery in 1973 of the 70-nm human rotavirus and its association with gastroenteritis in infants and young children represent major recent advances in the long and elusive search for etiologic agents of acute infectious nonbacterial gastroenteritis. Rotaviruses have emerged as the single most important etiologic agents of serious diarrheal illness of infants and young children under 2 years of age in almost all developed and developing countries where appropriate studies have been performed. In most populations studied, rotaviruses have been associated with 35-50% of severe diarrheal disease occurring in infants and children under 2 years of age, who require hospitalization.
It is clear from a number of studies that rotaviruses are responsible for a significant proportion of serious diarrheal illness. Hence, a rotavirus vaccine is an obvious necessity in both the developing and the developed countries as a prophylactic measure against rotavirus diseases.
Several approaches to the development of a live rotavirus vaccine have been pursued. Two approaches that have been evaluated in humans include (1) the use of a live attenuated human rotavirus strain and (2) the use of a rotavirus strain of animal origin. The rationale for the second approach, the use of an animal rotavirus as a candidate vaccine for humans, has been suggested by several studies. First, animal and human rotaviruses share a common group antigen and second, calves immunized in utero with the bovine NCDV strain were resistant to challenge with a human rotavirus serotype-1 strain shortly after birth (Wyatt et al. 1979. Science 203:548). As previously reported by Vesikari et al. (Lancet 1:977 1984), oral administration of the bovine rotavirus NCDV strain (RIT 4637) induced resistance in infants and young children against moderate or severe diarrheal illness caused by human rotavirus.
It should be noted, however, that there are at least four known serotypes of human rotavirus. These are designated serotypes 1-4, respectively. Of these, serotypes 1 and 3 are the most important rotavirus serotypes with respect to human disease. In contrast, the bovine rotavirus used in some vaccines belongs to serotype 6 which has not yet been found in humans. Hence, a need obviously exists for the production of a vaccine which would provide immunity against infection from human rotaviruses belonging to all serotypes but more specifically against serotypes 1 and 3 which are the most pathogenic of the human rotaviruses.